Trial document





This trial has been registered retrospectively.
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  DRKS00006345

Trial Description

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Title

Clinical and neurobiological effects of NIRS-controlled transcranial magnetic stimulation
(rTMS) in patients with panic disorder during cognitive behavioural therapy (CBT) treatment

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Trial Acronym

[---]*

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URL of the Trial

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Brief Summary in Lay Language

A number of scientific studies suggests that a particular brain region (the so called amygdala) may be hyperactive in patients with panic disorder. At the same time, it can be assumed that parts of the cerebral cortex belonging to the forebrain - the so called prefrontal cortex - which is meant to inhibit the amygdala, is less activated in patients with anxiety disorders. Cognitive behavioural therapy has been shown to be the most effective form of psychotherapy to treat panic disorder. Interestingly, it has been revealed that cognitive behavioural therapy is able to normalise the hyperactivity of the amygdala as well as the hypoactivity of the prefrontal cortex. Moreover, a method called repetitive transcranial magnetic stimulation is known to increase or decrease the activity of specific brain regions via magnetic impulses. Near-infrared spectroscopy on the other hand, is a technology which allowes to investigate the blood flow in the brain in a non-invasive manner. To do so, small sensors (called optodes) are integrated into a rubber cap which is adjuted to the head. This way, only harmless light of defined wave lengths is emited and the the amount of reflected light is measured. In doing so, blood flow changes can be recored which in turn refer to the extent of ongoing brain activity. In our study we want to find out if it is possible to optimise the outcome of cognitive behavioural therapy by promoting the activity of the prefrontal cortex by means of repetitive transcranial magnetic stimulation. If the prefrontal cortex is more active, it should be able to better inhibit the amygdala which should finally lead to a reduction of excessive fear. This effect should not only be reavealing inself by an improvement of panic disorder symptoms but also by changes in the brain blood flow (as measured by near-infrared spectroscopy). Additionally, it is planed to comapre the group of panic disorder patients with a healthy control group that does not receive any treatment with respect to their brain activation.

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Brief Summary in Scientific Language

Panic disorder (PD) belongs to the most frequent and disabling psychiatric disorders. Studies investigating neurobiological mechanisms of PD have suggested that clinical symptoms of PD such as sudden unexpected panic attacks might be the result of a dysfunction of the fear network including hyperactivity of the amygdala and decreased activity of the prefrontal cortex. Accordingly, a neurobiological model of inadequate top-down governance in anxiety disorders has been established. Cognitive behavioral therapy (CBT), which is currently recommended the most effective psychotherapeutic approach might modulate and restitute this dysfunctional network. As revealed by fMRI data, cognitively oriented psychotherapy is capable to affect fear-relevant neuronal circuits such as corticolimbic pathways and has been shown to normalise both exaggerated amygdala activity and prefrontal hypofunction. However, although effective in many patients, the use of CBT is often hampered by insufficient and slow response or a delayed onset of action. Moreover, additional psychopharmacological medication is needed in many cases for adequate clinical management. Therefore it was hypothesised, whether focal activation of the prefrontal cortex using the method of repetitive transcranial magnetic stimulation (rTMS) would be a promising strategy to augment effects of CBT in these patients by targeting key areas of the fear network involved in therapeutic action of CBT. For this purpose, sham-controlled add-on rTMS will be administered in 40 patients with PD receiving a course of state-of-the-art CBT. In order to examine both clinical and neurobiological effects of rTMS in these patients during psychotherapy apart from clinical outcome measures, near-infrared spectroscopy in combination with emotional or cognitive tasks will be applied before and after rTMS treatment for simultaneous control of prefrontal cortical activity. This data will further be compared to the brain activation patterns of a healthy control group that does not receive any treatment.The study might thus provide insight into the neurobiological mechanisms and changes in panic patients treated with CBT and rTMS and open up new perspectives for the combination of psychotherapeutic and neurobiological treatment strategies.

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Organizational Data

  •   DRKS00006345
  •   2014/07/21
  •   [---]*
  •   yes
  •   Approved
  •   2010-376-f-S, Ethik-Kommission der Ärztekammer Westfalen-Lippe und der med. Fakultät der Westfälischen Wilhelms-Universität Münster
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   F41.0 -  Panic disorder [episodic paroxysmal anxiety]
  •   F40.01 -  [generalization F40.0: Agoraphobia]
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Interventions/Observational Groups

  •   9 weeks of CBT - 1.5 hours/week, average group size 5 participants + verum iTBS (intermittend thetaburst stimulation, Huang et al., 2005: 600 pulses applied in intermittent biphasic bursts at a
    frequency of 15 pulses per second via 2 second trains, starting every 10 seconds leading to a stimualtion time of approximately 3.7 minutes) -15 sessions within the first 3 weeks, monday till friday, respectively
  •   9 weeks of CBT - 1.5 hours/week, average group size 5 participants + sham iTBS (intermittend thetaburst stimulation, Huang et al., 2005) -15 sessions within the first 3 weeks, monday till friday, respectively
  •   Additionally, comparison to healthy control group which does not receive any intervention but only showes up twice for the measurement of prefrontal brain activation as well as questionnaire completion within the same time interval (three weeks) as the patients.
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo, Other
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

clinical symptom severity: measured by means of the German version of the Panic and Agoraphobia scale (PAS; Bandelow, 1997), the Hamilton Anxiety Rating Scale (HAM-A; Hamilton, 1996) and the Cardiac Anxiety Questionnaire (CAQ; Eifert et al., 2000; Hoyer et al., 2005) at the following dates:
- at the begining of rTMS (repetitive transcranial magnetic stimulation) treatment
- after the first week of rTMS treatment
- after the second week of rTMS treatment
- at the end of rTMS treatment
- after nine weeks, to say at the end of CBT (cognitive behavioural therapy)
- at the first follow-up date three months after the end of CBT
- at the second follow-up date six months after the end of CBT

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Secondary Outcome

prefrontal brain activation: measured by means of near-infrared spectroscopy, at the latest 48 hours before the first rTMS treatment and at the earliest 12 hours afte the last rTMS treatment

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2011/01/12
  •   70
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   65   Years
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Additional Inclusion Criteria

DSM-IV Diagnosis of Panic Disorder with or without Agoraphobia

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Exclusion Criteria

Any severe somatic disorder · Brain organic disorder · Substance abuse disorder · Schizophrenia · Schizoaffective disorder · Bipolar disorder · Severe major depression · Severe Personality Disorders (e.g Borderline personality disorder) · Suicidality · Epilepsy · Cardiac Pacemaker · Any metal parts within the head · past or current benzodiazepine treatment within 3 half-lives before study begin · past or current treatment with anticonvulsiva during the last 3 months · pregnancy

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Addresses

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    • Universitätsklinikum Münster
    • Domagkstraße 5
    • 48149  Münster
    • Germany
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    • Klinik für Psychiatrie und Psychotherapie
    • Mr.  Prof.  Andreas  Fallgatter 
    • Calwerstr. 14
    • 72076  Tübingen
    • Germany
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    • Klinik für Psychiatrie und Psychotherapie, Tübingen
    • Ms.  Saskia  Deppermann 
    • Calwerstr. 14
    • 72076  Tübingen
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung Dienstsitz Bonn
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2013/10/21
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Trial Publications, Results and other Documents

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